Thanks for the kind words, Jake.
However, in that post I quoted a whole lot from an AI response to an extended line of inquiry. So it was AI—not me—who said “CYDY added CCL2 to the protocol as a defensive screen.” That is AI making an educated guess that adding CCL2 to the testing protocol is to make sure the tumors aren’t using CCR2 as a work-around to CCR5 blockade… as a “back door to maintain its immunosuppressive shield.” And this line of inquiry goes back to the much-discussed addition of CCL2/3/4 to the trial protocol a couple months ago. Given the redundancy of the immune system, testing for CCL2/3/4 seems like the smart thing to do. And the CYDY team is pretty smart… so I think AI is right about this.
As far as expecting great ORR and OS data in the current mCRC trial, first thing is the 60% response rate in the earlier basket trial. And that didn’t include an ICI! In addition, the current ctDNA numbers look really great, even though most of what we’ve seen is with a sub-optimal dose. Gotta believe the good Dr Kasi here, and he seems excited. Perhaps there is an additive or synergistic effect with the anti-angiogenic Avastin… and/or the chemo? That is why I’m optimistic about the pre-ICI patient results… compared to the Standard of Care, anyway. Weren’t there reports that Quality of Life is improving in patients? That would be another encouraging sign. I do wonder about durability of response though, and hope they get an ICI sooner than later.
My only question about the trial would be—what if we get a lot of partial responses and stable disease over the limited time-frame of the trial? We won’t get to see a lot of progression and thus not a lot of the LL/ICI combo. But with the EAP in TNBC we should see the combo do it’s thing, and I’m expecting dramatic results there. We don’t really know what the DSMB will do in the mCRC trial, though. Like when PD-L1 numbers hit the magic mark—are they going to get an ICI right then? A lot of this is in the hands of the DSMB. I sure wouldn’t want to die for science…
Since the Zhao/Liu paper just came out like 3 days ago, I don’t think the Cytodyn team was using that information to pre-screen or anything like that. But maybe they are using that data now! You gotta figure they are paying attention. Anyway, the whole point of the exercise was to explore the implications of that paper and see what AI had to say about CCL3/4 as a potential biomarker. Daniel Adams and Creatv Micro Tech are probably all over the new info; they just need to figure out the appropriate threshold and timing. The FDA loves it when you can pair the use of a therapeutic with a biomarker. This quote bears repetition “Finding this biomarker signature creates a definitive, data-driven mandate to prescribe leronlimab.” That is freaking HUGE! It makes it easy on the FDA… easy on oncologists… and at under $200/test, it makes it easy on Medicare! So yeah, I guess you could say this all makes me even more optimistic.
It’s not like I don’t get antsy sometimes… Especially now, with ASCO and all the news about successful drugs in pancreatic cancer, even RAS mutations. But even though there is progress, if you double or triple efficacy from a low baseline, it’s really just incremental improvement, no matter how the medical establishment frames it. Now 5 out of 5, 5 years on… No Evidence of Disease! If the numbers come anywhere close, that is the only Revolution anyone is going to be talking about next ASCO. A lotta people won’t believe it. Big Pharma will be shitting in their pants, and bidding up the price if they have any sense. If not… well, revolutions have consequences.
As far as the Ohm comment—Stifle Yourself! That is sacrilege. If I was a nun I’d rap your knuckles a hundred times with a ruler… and send you away for a thousand Hail Mary’s! And I’m not even Catholic. So cut that out.
However, in that post I quoted a whole lot from an AI response to an extended line of inquiry. So it was AI—not me—who said “CYDY added CCL2 to the protocol as a defensive screen.” That is AI making an educated guess that adding CCL2 to the testing protocol is to make sure the tumors aren’t using CCR2 as a work-around to CCR5 blockade… as a “back door to maintain its immunosuppressive shield.” And this line of inquiry goes back to the much-discussed addition of CCL2/3/4 to the trial protocol a couple months ago. Given the redundancy of the immune system, testing for CCL2/3/4 seems like the smart thing to do. And the CYDY team is pretty smart… so I think AI is right about this.
As far as expecting great ORR and OS data in the current mCRC trial, first thing is the 60% response rate in the earlier basket trial. And that didn’t include an ICI! In addition, the current ctDNA numbers look really great, even though most of what we’ve seen is with a sub-optimal dose. Gotta believe the good Dr Kasi here, and he seems excited. Perhaps there is an additive or synergistic effect with the anti-angiogenic Avastin… and/or the chemo? That is why I’m optimistic about the pre-ICI patient results… compared to the Standard of Care, anyway. Weren’t there reports that Quality of Life is improving in patients? That would be another encouraging sign. I do wonder about durability of response though, and hope they get an ICI sooner than later.
My only question about the trial would be—what if we get a lot of partial responses and stable disease over the limited time-frame of the trial? We won’t get to see a lot of progression and thus not a lot of the LL/ICI combo. But with the EAP in TNBC we should see the combo do it’s thing, and I’m expecting dramatic results there. We don’t really know what the DSMB will do in the mCRC trial, though. Like when PD-L1 numbers hit the magic mark—are they going to get an ICI right then? A lot of this is in the hands of the DSMB. I sure wouldn’t want to die for science…
Since the Zhao/Liu paper just came out like 3 days ago, I don’t think the Cytodyn team was using that information to pre-screen or anything like that. But maybe they are using that data now! You gotta figure they are paying attention. Anyway, the whole point of the exercise was to explore the implications of that paper and see what AI had to say about CCL3/4 as a potential biomarker. Daniel Adams and Creatv Micro Tech are probably all over the new info; they just need to figure out the appropriate threshold and timing. The FDA loves it when you can pair the use of a therapeutic with a biomarker. This quote bears repetition “Finding this biomarker signature creates a definitive, data-driven mandate to prescribe leronlimab.” That is freaking HUGE! It makes it easy on the FDA… easy on oncologists… and at under $200/test, it makes it easy on Medicare! So yeah, I guess you could say this all makes me even more optimistic.
It’s not like I don’t get antsy sometimes… Especially now, with ASCO and all the news about successful drugs in pancreatic cancer, even RAS mutations. But even though there is progress, if you double or triple efficacy from a low baseline, it’s really just incremental improvement, no matter how the medical establishment frames it. Now 5 out of 5, 5 years on… No Evidence of Disease! If the numbers come anywhere close, that is the only Revolution anyone is going to be talking about next ASCO. A lotta people won’t believe it. Big Pharma will be shitting in their pants, and bidding up the price if they have any sense. If not… well, revolutions have consequences.
As far as the Ohm comment—Stifle Yourself! That is sacrilege. If I was a nun I’d rap your knuckles a hundred times with a ruler… and send you away for a thousand Hail Mary’s! And I’m not even Catholic. So cut that out.
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